RECOMBINANT APROTININ IN CORONARY-ARTERY BYPASS GRAFT OPERATIONS

Objective: To evaluate the role of recombinant bovine aprotinin in red ucing blood loss in coronary artery bypass graft surgery. Design: An o pen-label, randomized, controlled study evaluating two dosage levels o f recombinant aprotinin, Setting: Two acute care hospitals (Northweste rn Memorial Hospital, Chicago, III,, and the Scott & White Memorial Ho spital, Temple, Texas), Patients: Patients undergoing primary and reop eration coronary artery bypass grafting were assigned to groups by mea ns of a computer-generated table of random numbers, Treated (n = 48) a nd control (n = 36) patients did not differ significantly in age, sex, weight, number of grafts, or preoperative hemoglobin level. Intervent ions: Recombinant aprotinin was given at two dosages, Dosage level 1 c onsisted of a bolus of 2 mg/kg intravenously immediately after the ind uction of anesthesia, 1 mg/kg added to each liter of the oxygenator pr ime, and 0.5 mg . kg(-1). hr(-1) infused continuously during operation , At dosage level 2, doses were doubled, Intraoperative monitoring of anti-factor Xa activity was performed, and additional doses of heparin were given on the basis of anti-factor Xa results, Main outcome measu res: Preoperative and postoperative hemoglobin levels, amounts of auto transfusion device and chest tube drainage blood, and transfusions of allogeneic red blood cells, Adverse clinical events (alterations in re nal function, graft thrombosis, myocardial infarction, and death) were recorded, Results: Additional heparin was given to 48% patients in th e aprotinin group and to 44% of control patients, Overall red blood ce ll loss (in milliliters, mean +/- standard deviation [SD]) was decreas ed with aprotinin at dosage level 1 for reoperations (1040 +/- 162 vs 1544 +/- 198, p < 0.01), and at dosage level 2 for all operations (pri mary operations, 886 +/- 362 vs 1333 +/- 618, p = 0.02; reoperations, 1191 +/- 560 vs 1815 +/- 1116, p = 0.2), Fewer patients in the aprotin in than in the control group had transfusions of donated blood (6/48 v s 12/36, p = 0.02) or reinfusion of chest tube drainage blood (12/48 v s 20/36, p < 0.01), Among patients receiving dosage level 1, there wer e no myocardial infarctions or deaths, At dosage level 2, one patient had profound bradycardia and died on day 12 and two patients had late graft closures, Two control patients had hypotension after bypass nece ssitating intraaortic balloon pumps, and one of these patients died, P ostoperative increases in blood urea nitrogen and creatinine levels we re small in both aprotinin and control groups. No hypersensitivity or other allergic reactions occurred, Conclusion: We conclude that, at th e dosages given, recombinant bovine aprotinin decreases surgical blood loss and transfusion requirements in patients undergoing coronary art ery bypass grafting, but its use requires appropriate monitoring of he parin use during bypass. Whether higher dosages of aprotinin increase the risk of graft thrombosis must be further assessed with a larger pa tient sample.